Effect of Amrinone, a cardiotonic drug, on hemodynamics and platelet function.
In the present study we have investigated the effect of Amrinone on the hemodynamics, platelet counts, prostacyclin and thromboxane synthesis and platelet function. Results show that infusion of the drug increased the heart rate and lowered left atrial, aortic and pulmonary artery pressures within five minutes after a single bolus injection of 2 mg/kg IV dose. Platelet counts made from the blood obtained from anesthetized dogs after the drug infusion showed severe loss of platelets. However, infusion of a similar dose in awake dogs showed no such detrimental effect on platelets. Examination of formalin fixed blood for aggregates showed no more clumps in the treated samples than in the control. Platelets obtained from canine blood drawn at 30 minutes post infusion of the drug showed no aggregatory response to arachidonate. However, the response of these platelets to ADP was quite normal. Amrinone infusion had no inhibitory effect on the ability of vascular tissue to convert arachidonic acid to prostacyclin. Similarly, no inhibitory action could be observed on platelet cyclo-oxygenase activity at this concentration (2 mg/kg). In vitro studies on human platelets showed significant inhibition of cyclo-oxygenase at high concentrations (0.5 mg/ml). Therefore it is unlikely that the drug caused inhibition of the platelet response to arachidonate by the inhibition of prostaglandin synthesis during infusion, as the dose used was quite low (2 mg/kg) compared to what is required for the inhibition of cyclo-oxygenase.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000631:Aminopyridines; D000676:Amrinone; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000096:biosynthesis; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis
D000631:Aminopyridines; D001095:Arachidonic Acids; D002316:Cardiotonic Agents; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D000676:Amrinone